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1.
To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.  相似文献   

2.
To investigate the inhibiting effect of β-Aescin on nuclear factor-κB(NF-κB)activation and the expression of tumornecrosis factor-α(TNF-α)protein after traumatic brain injury(TBI)in the rat brain,62 SD rats were subjected to lateral corticalimpact injury caused by a free-falling object and divided randomly into four groups:(1)sham operated(Group A);(2) injured(Group B);(3)β-Aescin treatment(Group C);(4) pyrrolidine dithocarbamate(PDTC) treatment(Group D).β-Aescin was ad-ministered in Group C and PDTC treated in Group D immediately after injury.A series of brain samples were obtained directly 6h,24 h and 3 d respectively after trauma in four groups.NF-κB activation was examined by Electrophoretic Mobility Shift Assay(EMSA);the levels of TNF-α protein were measured by radio-immunoassay(RIA);the water content of rat brain was measuredand pathomorphological observation was carried out.NF-κB activation,the levels of TNF-α protein and the water content of ratbrain were significantly increased(P＜0.0  相似文献   

3.
Objective: To assess the effect of angiotensin Ⅱ type 1 (AT1) receptor antagonist losartan on myocardium connexin43 (Cx43) gap junction (GJ) expression in spontaneously hypertensive rats (SHRs) and investigate possible mechanisms. Methods: Sixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto (WKY) rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30mg/(kg·d) by oral gavage once daily for 8 weeks (SHR-L) or vehicle (0.9% saline) to act as controls (SHR-V); WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 (NF-κB p65) proteins in all three groups were observed and further investigations on the effect of angiotensin Ⅱ type 1 receptor antagonist losartan (30mg/(kg·d), 8 weeks) on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-κB p65 protein in nuclear extracts was determined by Western blot. Results: Left ventricular (LV) hypertrophy was prominent in SHRs, Cx43 and NF-κB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-κB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment. Conclusion: Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin Ⅱ type l receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-κB pathway.  相似文献   

4.
Objective: This study is to determine the effect of the natural product parthenolide, a sesquiterpene lactone isolated from extracts of the herb Tanacetum parthenium, on the proliferation of vascular smooth muscle cells (VSMCs). Methods: Rat aortic VSMCs were isolated and cultured in vitro, and treated with different concentrations of parthenolide (10, 20 and 30 μmol/L).[3H]thymidine incorporation was used as an index of cell proliferation. Cell cycle progression and distribution were determined by flow cytometric analysis. Furthermore, the expression of several regulatory proteins relevant to VSMC proliferation including IκBα, cyclooxygenase-2 (Cox-2), p21, and p27 was examined to investigate the potential molecular mechanism. Results:Treatment with parthenolide significantly decreased the [3H]thymidine incorporation into DNA by 30%～56% relative to control values in a dose-dependent manner (P＜0.05). Addition of parthenolide also increased cell population at G0/G1 phase by 19.2%～65.7% (P＜0.05) and decreased cell population at S phase by 50.7%～84.8% (P＜0.05), which is consistent with its stimulatory effects on p21 and p27. In addition, parthenolide also increased IκBα expression and reduced Cox-2 expression in a time-dependent manner. Conclusion: Our results show that parthenolide significantly inhibits the VSMC proliferation by inducing G0/G1 cell cycle arrest. IκBα and Cox-2 are likely involved in such inhibitory effect of parthenolide on VSMC proliferation. These findings warrant further investigation on potential therapeutic implications of parthenolide on VSMC proliferation in vivo.  相似文献   

5.
Objective: To observe the difference of androgen and inflammatory cytokines level in atherosclerosis and analyse their relations. Method: Both carotid arteries and arteries of lower extremity were subjected to ultrasonic examination by Doppler's method. Those with much atheromatous plaque formation were ranged into case group, and those with normal result formed control group. Total, free testosterone and estradiol were assayed by radioimmunoassay. C reactive protein (CRP) was assayed by nepheloturbidity. Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Interleukin- 18 (IL- 18), soluble intercellular adhesion molecule- 1 (sICAM- 1) and soluble vascular cell adhesion molecule- 1 (sVCAM- 1)were assayed by ELISA. The mean difference between two groups and the correlation between free testosterone and cytokines were analysed. Results: Free testosterone was (6.337±3.371) pg/L in case group and (11.375±4.733) pg/L in control group, P＜0.01.No differences were found in total testosterone and estradiol. CRP was (27.294±10.238) mg/L in case group and (12.843±6.318)mg/L in control group, P＜0.01. IL-6 was (41.700±31.385) pg/L in case group and (25.396±20.772) pg/L in control group, P＜0.05.IL-8 was (89.249±58.357) pg/L in case group and (67.873±31.227) pg/L in control group, P＜0.05. sICAM-1 was (470.491±134.078) pg/L in case group and (368.487±97.183) pg/L in control group, P＜0.01. sVCAM-1 was (537.808±213.172)pg/L in case group and (457.275±157.273) pg/L in control group, P＜0.05. There were no differences in TNF-α, IL-10 and IL-18.Correlation analysis showed that FT (free testosterone) had negative correlation with CRP, IL-6 and sICAM-1. Among them FT had well correlation with CRP, correlation index was -0.678. Conclusion: Free testosterone was in negative correlation with atherosclerosis in old-age male. Free testosterone may have the role of anti-atherosclerosis, and this effect was not achieved by its transformation to estradiol. Low free testosterone level was followed by increased level of inflammatory cytokines. Low free testosterones coexist with inflammation and they both affect the process of atherosclerosis in old-age male.  相似文献   

6.
Objective: To investigate the immunological function of a yeast expression system for thymosin α1(Tα1). Methods: A constructed Tα1 yeast expression system was used to investigate the immunological function of orally administered Tα1. Dried yeast containing three different concentration of Tα1 was fed to normal Balb/c mice and other Balb/c mice whose immunities were inhibited in advance by cyclophosphamide. Synthesized Tα1 peptide was used as positive control and dried yeast with empty plasmid was used as negative control. CD4 and CD8 levels were detected by flow cytometry assay. TNF-α IFN-γ IL-2, IL-6 and IL-10 levels were detected by liquid chip. Results: In normal Balb/c mice or immune inhibition Balb/c mice, CD8 levels were significantly increased. Especially in immune inhibition Balb/c mice, CD8 levels in synthesized Tα1 group (18.77％±4.72％),small dose group (13.48％±6.17％) and large dose group (22.74％±1.09％) were significantly higher than that in empty yeast control group (7.49％±2.14％). Conclusion: Orally administered Tα1 has its certain immunomodulatory function.  相似文献   

7.
Objectives:Severe acute pancreatitis(SAP) can lead to acute lung injury(ALI) .The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI in rats with SAP.Methods:The thin film method was used to prepare liposomes.Sprague-Dawley rats were randomly divided into three groups.After the SAP model was established by injecting 5%(w/v) sodium taurocholate(2 ml/kg body weight) into the subcapsular space of the pancreata,normal saline was administered to the control(C) group,phosphate buffer solution(PBS) -containing liposome to the Pgroup,and clodronate-containing liposome to the Tgroup through tail veins.Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase,interleukin-6(IL-6) ,and tumor necrosis factor-α(TNF-α) .Morphological changes in the pancreata and lung were observed using hematoxylin and eosin(HE) staining,while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) .In addition,the macrophage marker cluster of differentiation 68(CD68) in lung tissue was detected with immunohistochemistry.Results:Blood levels of amylase,IL-6,and TNF-αwere significantly increased in the Pgroup compared to those in the Tgroup(P0.05) .In the Tgroup,large numbers of TUNEL-positive cells were observed,but no or few in the C and Pgroups.Gross inspection and HE staining of pancreata and lung showed dramatic tissue damage,including inflammation and necrosis in the Pgroup.Less remarkable changes were noted in the Tgroup,and the C group exhibited normal histology.The histological scores according to Kaiser's criteria were consistent with HE findings.The number of CD68-positive macrophages decreased in the Tgroup.Conclusions:Clodronate-containing liposomes have a protective effect against ALI in rats with SAP.Blockade of macrophages may represent a novel therapeutic strategy in SAP.  相似文献   

8.
Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine(BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3 T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3 T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide(MTT)assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3 T3-E1 cells were increased,as established by the alkaline phosphatase(ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test,and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK(receptor activator of nuclear factor-κB(NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.  相似文献   

9.
Hydrophilic degraded gelatin was modified with hydrophobic poly(ε-caprolactone) (PCL) via a chemical grafting route.Firstly,PCL with one hydroxyl end group was prepared by the ring-opening polymerization of εcaprolactone (ε-CL) with tin (Ⅱ) 2-ethylhexanoate as catalyst and n-butyl alcohol as initiator.Secondly,the PCL reacted with isophorone diisocyanate (IPDI) to prepare PCL with isocyanate functional group (PCL-NCO).Hydroxylamine was used to degrade gelatin by the cleavage between asparagine and glycine residues of gelatin.PCL-NCO reacted with the hydroxyl/amino groups of degraded gelatin in a homogeneous system and yielded the PCL modified gelatin copolymers.The gelatin grafted PCL copolymers were measured by means of XRD,FTIR,DSC and 1 H NMR.The results confirmed the conjugation of PCL onto gelatin chains.The PCL modified gelatin can be used as biomaterials owing to their biocompatibility and biodegradation.  相似文献   

10.
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11.
Objective： Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Methods： Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was per- formed with normal saline （group B）, vitamin C （group C） and vitamin E （group D）. Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline （sample B）, vitamin C （sample C） and vitamin E （sample D）. Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression. Results： In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only, and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Conclusion： Vitamin C can protect vascular endothelial cells from mannitol-induced injury.  相似文献   

12.
Objective: The age-related change is important part of degenerative disc disease. However, no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods: 22-month-old Sprague-Dawley (SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types Ⅱ and Ⅹ was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed.Results: There were less collagen type Ⅱ expression and more collagen type Ⅹ expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased, compared with that of the young control group (P＜0.01). Conclusion: Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types Ⅱ and Ⅹ, numbers and areas of afferent vascular buds, the ratio of the non-calcified to the calcified layers, and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.  相似文献   

13.
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14.
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15.
Study on the neurotoxic effects of low-level lead exposure in rats   总被引：10，自引：0，他引：10  
Objective: To investigate effects of developmental lead exposure on nitric oxide synthase (NOS) activity in different brain regions and on N-methyl-D-aspartate (NMDA) receptor mRNA expression in the hippocampus of rats. On the basis of these observations, we explored possible mechanisms by which lead exposure leads to impaired learning and memorizing abilities in children. Methods: A series of rat animal models exposed to low levels of lead during the developing period was established (drinking water containing 0.025%, 0.05% and 0.075% lead acetate). NOS activities in the hippocampus, the cerebral cortex, the cerebellum and the brain stem were determined with fluorescence measurement and levels of mRNA expression of the NMDA receptor 2A (NR2A) subunit and NMDA receptor 2B (NR2B) subunit in the rat hippocampus were measured with Retro-translation (RT-PCR). Results: There were no differences in the body weight of rat pups between any of the groups at any given time (P>0.05). The blood lead level of Pb-exposed rat pups showed a systematic pattern of change: at 14 d of age, it was lower than that at 7 d of age, then rising to the peak level at 21 d and finally falling to lower levels at 28 d. The hippocampal NOS activities of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.01). NOS activities in the cerebellum of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.001) and the NOS activity of the 0.025% group was significantly lower than that of the 0.05% and 0.075% groups on the 28th day (P<0.05). NOS activity in the cerebral cortex of the 0.075% group was significantly lower than that of the control, 0.025% and 0.05% groups on the four day spans (P<0.001). There was no significant difference of NOS activity in the brain stem between any lead-exposed group and the control group on the four day spans. In the 0.05% and the 0.075% groups, the level of NR2A mRNA expression was higher than that in the control group at 7 d and 14 d of age (P<0.05). In the 0.025% group, the level of NR2A was found to be higher than that in the control group at 7 d of age only (P<0.05). No significant differences were found for the levels of NR2B mRNA expression between any of the groups at any given time. Conclusions: NOS activity in the hippocampus, the cerebral cortex and the cerebellum are inhibited by lead exposure. The degree of the inhibitory effect depends on the time span of exposure and the lead concentration. Developmental low-level lead exposure was found to raise the level of NR2A mRNA expression in the hippocampus of rats. Developmental low-level lead exposure does not affect the level of NR2B mRNA expression in the hippocampus.  相似文献   

16.
Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.  相似文献   

17.
Objective: To evaluate the expression of matrix metalloproteinase-9 (MMP9) in nasopharyngeal carcinoma and the association between MMP9 and Epstein-Barr virus infection. Methods: The MMP9 expression was studied by immu-nohistochemical analysis; and Epstein-Barr virus encoded small nuclear mRNA-1(EBER-1) produced by in situ hybridization were examined in 41 nasopharyngeal carcinoma sections, and the relation between them, and the associations of MMP9 with clinical features were statistically analyzed. Results: Positive expression rate of MMP9 was 73.17%. The expression of MMP9 showed significant positive correlation with the expression of EBER-1 (γ0.483, P=0.001). There was significant association of MMP9 expression with lymph nodes metastasis and clinical stage (P<0.001), non-significant association with age, gender, pathological classification and T classification. Conclusions: The highly pronounced expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus can enhance N  相似文献   

18.
The lipase activities in the three main Chinese castor bean varieties [ZiBi 05 （ZB 5）,TongBi 06 （TB 6）,JinBi 02 （JB 2）] were investigated.Two lipases were found in extracts from the endosperms of all the three varieties.One lipase is located in the lipid bodies,showing higher activity at pH 4.5 and exhibiting the highest activity at day 1 of germination.The other lipase is located in the particulates,showing higher activity at pH 9.5 and particularly active at day 4 of germination.The lipid bodies from ZB 5 show the highest lipase activity at day 1 and pH 4.5 among the three varieties during the 8 d of germination.The acid lipase located in the lipid bodies of ZB 5 of germination 1 d was purified to homogeneity by DEAE-sepharose CL-6B and butyl-sepharose CL-4B chromatography after isolation,delipidation and solubilization,with a purification factor of 16.1 and overall activity recovery of 17.7%.The characterizations （such as optimum pH,pH stability,optimum temperature,thermal stability,effect of metal ions,organic solvents stability,substrate specificity） of the purified acid lipase were conducted in detail.A combination of the characterized properties may make this enzyme a useful biocatalyst for industrial application.  相似文献   

19.
Objective: To establish normally conditionally-immortalized human umbilical vein endothelial cells (HUVECs) by ectopic expression of the human telomerase catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. Methods: Primary HUVECs were transfected with recombinant retrovirus containing hTERT or SV40 LT respectively. Subsequently drug resistant cell clones were screened and expanded for further studies. Endothelial cell biomarkers were confirmed by examination. Results: The morphological phenotype of the transfected cells was similar to the non-transfected cells. Von Willebrand factor, hTERT and SV40 LT could be detected in transfected HUVECs. Moreover, higher telomerase activity in transfected cells was maintained for over 50 population doublings compared with only low level of endogenous telomerase transiently at early population doublings in primary HUVECs. When exposed to TNF-α(tumor necrosis factor-α), the expression of E-selectin in transfected cells was significantly up-regulated, but no alteration of endothelial lipase was found. Conclusion: Ectopic coexpression of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in vitro. Immortalized HUVECs may be an ideal target of further molecular function studies.  相似文献   

20.
Samples of sufu, a traditional food product made by fermenting soybeans, were collected in the city of Anshun in Southwest China and their bacterial diversity was investigated. Nine samples were divided into groups A–C, according to the markets in which they were collected, and the samples were subjected to pyrosequencing of the 16 S rRNA V3–V4 regions for evaluation of the bacterial community. A total of 342 operational taxonomic units(OTUs) were determined. One of the samples(B2) included as many as 286 OTUs, and it also displayed the greatest bacterial richness. The most abundant bacterial diversity was shown in group B. Firmicutes was the dominant phylum in groups A and B, while Proteobacteria was the dominant phylum in group C. Lactobacillus was the prevailing genus in group A, Tetragenococcus in group B, and Empedobacter in group C. The bacterial composition of sufu depends, to a large degree, on the manufacturer. The obtained results showed regional differences in the bacterial community patterns of sufu products, which could contribute to a better understanding of the fermentation and ripening bioprocesses of sufu.  相似文献   

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